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Molecular and Cellular Biology

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https://www.readbyqxmd.com/read/28320876/taking-a-step-back-from-back-translocation-an-integrative-view-of-lepa-ef4-s-cellular-function
#1
Jalyce L E Heller, Rajashekhar Kamalampeta, Hans-Joachim Wieden
Protein synthesis, the translation of mRNA into a polypeptide facilitated by the ribosome, is assisted by a variety of protein factors, some of which are GTPases. In addition to four highly conserved and well-understood GTPases with known function, there are also a number of non-canonical GTPases that are implicated in translation but whose functions are not fully understood. LepA/EF4 is one of these non-canonical GTPases. It is highly conserved and present in bacteria, mitochondria and chloroplasts, but its functional role in the cell remains unknown...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28320875/gata3-abundance-is-a-critical-determinant-of-t-cell-receptor-beta-allelic-exclusion
#2
Chia-Jui Ku, JoAnn M Sekiguchi, Bharat Panwar, Yuanfang Guan, Satoru Takahashi, Keigyou Yoh, Ivan Maillard, Tomonori Hosoya, James Douglas Engel
Allelic exclusion describes the essential immunological process by which feedback repression of sequential DNA rearrangements ensures that only one autosome expresses a functional T or B cell receptor. In wild type mammals, approximately 60% of cells have recombined the DNA of one Tcrb V-to-DJ-joined allele in a functional configuration, while the second allele has only recombined the DJ sequences; the other 40% of the cells have recombined the V- to the DJ segments on both alleles, with only one of the two predicting a functional TCRβ protein...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28320874/enos-dependent-s-nitrosylation-of-%C3%AE-catenin-prevents-its-association-with-tcf4-and-inhibits-proliferation-of-endothelial-cells-by-wnt3a
#3
Ying Zhang, Rony Chidiac, Chantal Delisle, Jean-Philippe Gratton
Nitric oxide (NO) produced by endothelial NO synthase (eNOS) modulates many functions in endothelial cells. S-nitrosylation (SNO) of cysteine residues on β-catenin by eNOS-derived NO has been shown to influence intercellular contacts between endothelial cells. However, the implication of SNO in the regulation of β-catenin transcriptional activity is ill-defined. Here we report that NO inhibits the transcriptional activity of β-catenin and endothelial cell proliferation induced by activation of Wnt/β-catenin signaling...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28320873/sav1-loss-induces-senescence-and-stat3-activation-coinciding-with-tubulointerstitial-fibrosis
#4
Janet Y Leung, Harper L Wilson, Kristin J Voltzke, Lindsay A Williams, Hyo Jin Lee, Sara E Wobker, William Y Kim
Tubulointerstitial fibrosis (TIF) is recognized as a final phenotypic manifestation in the transition from chronic kidney disease (CKD) to end-stage renal disease (ESRD). Here, we show that conditional inactivation of Sav1 in the mouse renal epithelium resulted in upregulated expression of profibrotic genes and TIF. Loss of Sav1 induced Stat3 activation and a senescence-associated secretory phenotype (SASP) that coincided with the development of tubulointerstitial fibrosis. Treatment of mice with the YAP inhibitor, Verteporfin (VP), inhibited activation of genes associated with senescence, SASP and activation of Stat3 as well as impeded the development of fibrosis...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28320872/the-drosophila-daxx-like-protein-dlp-cooperates-with-asf1-for-h3-3-deposition-and-heterochromatin-formation
#5
Catherine Fromental-Ramain, Philippe Ramain, Ali Hamiche
Histone variants are non-allelic isoforms of canonical histones and they are deposited, in contrast to canonical histones, in a replication-independent (RI) manner. RI deposition of H3.3, a histone variant from the H3.3 family, is mediated in mammals by distinct pathways involving either the histone regulator A (HIRA) complex or the death-associated protein (DAXX)/α-thalassemia X-linked mental retardation protein (ATRX) complex. Here, we investigated the function of Drosophila DAXX Like Protein (DLP) by using both fly genetics approaches and protein biochemistry...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28320871/essential-roles-of-l-type-amino-acid-transporter-1-in-syncytiotrophoblast-development-by-presenting-fusogenic-4f2hc
#6
Ryuichi Ohgaki, Takahiro Ohmori, Saori Hara, Saya Nakagomi, Masami Kanai-Azuma, Kazuko Kaneda-Nakashima, Suguru Okuda, Shushi Nagamori, Yoshikatsu Kanai
Layer(s) of epithelial syncytium, syncytiotrophoblast, differentiates from chorionic trophoblasts via cell fusion and separates maternal and fetal circulations in hemochorial placentas. L-type amino acid transporter 1 (LAT1) and its covalently-linked ancillary subunit 4F2hc are colocalized on both maternal and fetal surface of syncytiotrophoblasts, implying their roles in amino acid transfer through the placental barrier. In this study, LAT1 knockout, in addition, revealed a novel role of LAT1 in syncytiotrophoblast development...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28289076/fumarate-mediates-a-chronic-proliferative-signal-in-fumarate-hydratase-inactivated-cancer-cells-by-increasing-transcription-and-translation-of-ferritin-genes
#7
Michael John Kerins, Ajay Vashisht, Benjamin Xi-Tong Liang, Spencer Jordan Duckworth, Brandon John Praslicka, James Akira Wohlschlegel, Aikseng Ooi
Germline mutations of the gene encoding the tricarboxylic acid cycle (TCA cycle) enzyme, fumarate hydratase (FH), cause a hereditary cancer syndrome known as hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC associated tumors harbor biallelic FH inactivation that results in the accumulation of the TCA cycle metabolite, fumarate. Although it is known that the fumarate accumulation can alter cellular signaling, if and how fumarate confers a growth advantage remains unclear. Here we show that fumarate accumulation confers a chronic proliferative signal by disrupting cellular iron signaling...
March 13, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28289075/coordinated-hsp110-and-hsp104-activities-power-protein-disaggregation-in-saccharomyces-cerevisiae
#8
Jayasankar Mohanakrishnan Kaimal, Ganapathi Kandasamy, Fabian Gasser, Claes Andréasson
Protein aggregation is intimately associated with cellular stress and is accelerated during aging, disease and cellular dysfunction. Yeast cells rely on the ATP-consuming chaperone Hsp104 to disaggregate proteins together with Hsp70. Hsp110s are ancient and abundant chaperones that form complexes with Hsp70. Here we provide in vivo data showing that yeast Hsp110s Sse1 and Sse2 are essential for Hsp104-dependent protein disaggregation. Following heat shock, complexes of Hsp110 and Hsp70 are recruited to protein aggregates and functions together with Hsp104 in the disaggregation process...
March 13, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28289074/t-cell-costimulation-by-cd6-is-dependent-on-bivalent-binding-of-a-gads-slp-76-complex
#9
Johannes Breuning, Marion H Brown
The cell surface receptor, CD6 regulates T cell activation in both an activating and inhibitory manner. The adaptor protein SLP-76 is recruited to the CD6 cytoplasmic phosphorylated Y662 residue during T cell activation, providing an activating signal to T cells. In this study, a biochemical approach identified the SH2 domain-containing adaptor protein GADS as the dominant interaction partner for the CD6 cytoplasmic Y629 residue. Functional experiments in human Jurkat and primary T cells showed that mutation of both Y629F and Y662F abolished costimulation by CD6...
March 13, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28265004/gain-of-function-mutation-of-tristetraprolin-impairs-negative-feedback-control-of-macrophages-in-vitro-yet-has-overwhelmingly-anti-inflammatory-consequences-in-vivo
#10
John D O'Neil, Ewan A Ross, Michael L Ridley, Qize Ding, Tina Tang, Dalya R Rosner, Thomas Crowley, Deepak Malhi, Jonathan L Dean, Tim Smallie, Christopher D Buckley, Andrew R Clark
The mRNA destabilizing factor tristetraprolin (TTP) binds in a sequence-specific manner to the 3' untranslated regions of many pro-inflammatory mRNAs and recruits complexes of nucleases to promote rapid mRNA turnover. Mice lacking TTP develop a severe, spontaneous inflammatory syndrome characterized by over-expression of tumor necrosis factor and other inflammatory mediators. However, TTP also employs the same mechanism to inhibit the expression of the potent anti-inflammatory cytokine interleukin 10. Perturbation of TTP function may therefore have mixed effects on inflammatory responses, either increasing or decreasing the expression of pro-inflammatory factors via direct or indirect mechanisms...
March 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28265003/sorla-in-interleukin-6-signaling-and-turnover
#11
Jakob Vejby Larsen, Claus Munck Petersen
Interleukin-6 (IL-6) is a multifunctional cytokine with important functions in various physiologic processes. Mice lacking IL-6 exhibit multiple phenotypic abnormalities such as an inadequate immune and acute-phase response, and elevated levels of circulating IL-6 have been found to accompany several pathologic conditions. IL-6 binds the non-signaling IL-6 receptor (IL-6R) - which is expressed as a transmembrane, as well as a secreted circulating protein - before it engages homodimeric gp130 for signaling. Complex-formation between IL-6 and the membrane-bound IL-6 receptor gives rise to classic cis-signaling, whereas complex-formation between IL-6 and the soluble IL-6R results in trans-signaling...
March 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28265002/deletion-of-pofut1-in-mouse-skeletal-myofibers-induces-muscle-aging-related-phenotypes-in-cis-and-in-trans
#12
Deborah A Zygmunt, Neha Singhal, Mi-Lyang Kim, Megan L Cramer, Kelly E Crowe, Rui Xu, Ying Jia, Jessica Adair, Isabel Martinez-Pena Y Valenzuela, Mohammed Akaaboune, Peter White, Paulus M Janssen, Paul T Martin
Sarcopenia, the loss of muscle mass and strength during normal aging, involves coordinate changes in skeletal myofibers and the cells that contact them, including satellite cells and motor neurons. Here we show that Protein O-fucosyltransferase 1 (Pofut1), a gene that encodes a glycosyltransferase required for NotchR-mediated cell-cell signaling, has reduced expression in aging skeletal muscle. Moreover, premature postnatal deletion of Pofut1 in skeletal myofibers can induce aging-related phenotypes in cis within skeletal myofibers and in trans within satellite cells and within motor neurons via the neuromuscular junction...
March 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28265001/phosphorylated-nuclear-receptor-car-forms-a-homodimer-to-repress-its-constitutive-activity-for-ligand-activation
#13
Ryota Shizu, Makoto Osabe, Lalith Perera, Rick Moore, Tatsuya Sueyoshi, Masahiko Negishi
Nuclear receptor CAR (NR1I3) regulates hepatic drug and energy metabolism as well as cell fate. Its activation can be a critical factor in drug-induced toxicity and disease development such as diabetes and tumors. CAR inactivates its constitutive activity by phosphorylation at threonine 38. Utilizing receptor for protein kinase 1 (RACK1) as the regulatory subunit, protein phosphatase PP2A dephosphorylates threonine 38 to activate CAR. Here we have demonstrated that CAR undergoes its homodimer-monomer conversion to regulate this dephosphorylation...
March 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28242652/glucose-deprivation-induces-atf4-mediated-apoptosis-through-trail-death-receptors
#14
Raffaella Iurlaro, Franziska Püschel, Clara Lucía León-Annicchiarico, Hazel O'Connor, Seamus J Martin, Daniel Palou-Gramón, Estefanía Lucendo, Cristina Muñoz-Pinedo
Metabolic stress occurs frequently in tumors and in normal tissues undergoing transient ischemia. Nutrient deprivation triggers, among many potential cell death-inducing pathways, an endoplasmic reticulum (ER) stress response with induction of the Integrated Stress Response transcription factor ATF4. However, how this results in cell death remains unknown. Here we show that glucose deprivation triggered ER stress and induced the Unfolded Protein Response transcription factors ATF4 and CHOP. This was associated with non-transcriptional accumulation of the TRAIL receptor TRAIL-R1 (DR4) and with ATF4-mediated, CHOP-independent induction of TRAIL-R2 (DR5), suggesting that cell death in this context may involve death receptor signaling...
February 27, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28223370/the-lim-only-protein-fhl2-is-a-negative-regulator-of-tgf-%C3%AE-1-expression
#15
Jennifer Dahan, Florence Levillayer, Tian Xia, Yann Nouët, Catherine Werts, Martine Fanton d'Andon, Minou Adib-Conquy, Anne-Marie Cassard-Doulcier, Varun Khanna, Ju Chen, Thierry Tordjmann, Marie-Annick Buendia, Grégory Jouvion, Yu Wei
TGF-β1 is a master cytokine in many biological processes including tissue homeostasis, epithelial to mesenchymal transition and wound repair. Here we report that the four and a half LIM-only protein 2 (FHL2) is a critical regulator of TGF-β1 expression. Devoid of DNA-binding domain, FHL2 is a transcriptional co-factor that plays the role of co-activator or co-repressor depending on the cell and promoter contexts. We detected association of FHL2 with the TGF-β1 promoter, which showed higher activity in Fhl2(-/-) cells than WT cells in a reporter assay...
February 21, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28223369/ssp2-binding-activates-the-smk1-mapk
#16
Chong Wai Tio, Gregory Omerza, Timothy Phillips, Hua Jane Lou, Benjamin E Turk, Edward Winter
Smk1 is a meiosis specific MAPK in S. cerevisiae that couples spore morphogenesis to the completion of chromosome segregation. Similar to other MAPKs, Smk1 is controlled by phosphorylation of a threonine (T) and tyrosine (Y) in its activation loop. However, it is not activated by a dual-specificity MAPK kinase. Instead, T207 in Smk1's activation loop is phosphorylated by the CDK-activating kinase (Cak1), and Y209 is autophosphorylated in an intramolecular reaction that requires the meiosis-specific protein, Ssp2...
February 21, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28223368/phosphatases-generate-signal-specificity-downstream-of-ssp1-kinase-in-fission-yeast
#17
Lin Deng, Mid Eum Lee, Katherine Schutt, James B Moseley
AMPK-related protein kinases (ARKs) coordinate cell growth, proliferation, and migration with environmental status. It is unclear how specific ARKs are activated at specific times. In fission yeast S. pombe, the CaMKK-like protein kinase Ssp1 promotes cell cycle progression by activating the ARK Cdr2 according to cell growth signals. Here, we demonstrate that Ssp1 activates a second ARK, Ssp2/AMPK-α, for cell proliferation in low environmental glucose. Ssp1 activates these two related targets by the same biochemical mechanism: direct phosphorylation of a conserved residue in the activation loop (Cdr2-T166 and Ssp2-T189)...
February 21, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28223367/coordination-of-myeloid-differentiation-with-reduced-cell-cycle-progression-by-pu-1-induction-of-micrornas-targeting-cell-cycle-regulators-and-lipid-anabolism
#18
Lauren A Solomon, Shreya Podder, Jessica He, Nicholas L Jackson Chornenki, Kristen Gibson, Rachel G Ziliotto, Jess Rhee, Rodney P DeKoter
During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26-transformation specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression...
February 21, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28223366/la-deletion-from-mouse-brain-alters-pre-trna-metabolism-and-accumulation-of-pre-5-8s-rrna-with-neuron-death-and-reactive-astrocytosis
#19
Nathan H Blewett, James R Iben, Sergei Gaidamakov, Richard J Maraia
Human La antigen (Sjögren's syndrome antigen B, SSB) is an abundant multifunctional RNA-binding protein. In the nucleoplasm, La binds to and protects from 3' exonucleases, the ends of precursor-tRNAs and other transcripts synthesized by RNA polymerase III, and facilitates their maturation, while a nucleolar isoform has been implicated in rRNA biogenesis by multiple independent lines of evidence. We showed earlier that conditional La knockout (La cKO) from mouse cortex neurons results in defective tRNA processing although pathway(s) involved in neuronal loss thereafter was unknown...
February 21, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28193847/dna-damage-response-independent-role-for-mdc1-in-maintaining-genomic-stability
#20
Zhiguo Li, Chen Shao, Yifan Kong, Colin Carlock, Nihal Ahmad, Xiaoqi Liu
MDC1 is a central player in checkpoint activation and subsequent DNA repair following DNA damage. Although MDC1 has been extensively studied, much of its known functions to date pertains to the DNA damage response (DDR) pathway. Herein, we report a novel function of phosphorylated MDC1, independent of ATM and DNA damage, which is required for proper mitotic progression and maintenance of genomic stability. We demonstrate that MDC1 is an in vivo target of Plk1 and that the phosphorylated MDC1 is dynamically localized to nuclear envelopes, centrosomes, kinetochores and the midbodies...
February 13, 2017: Molecular and Cellular Biology
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